Purpose: To investigate the potential of circulating-microRNAs (ct-miRNAs) as non-invasive biomarkers to predict the efficacy of single/dual HER2-targeted therapy in the NeoALTTO study. Experimental Design: Patients with plasma samples at baseline (T0) and/or after two weeks (T1) of treatment were randomized into training (n=183) and testing (n=246) sets. RT-PCR-based high-throughput miRNA-profiling was employed in the training set. After normalization, ct-miRNAs associated with pathologic Complete Response (pCR) were identified by univariate analysis. Multivariate logistic regression models were implemented to generate treatment-specific signatures at T0 and T1, which were evaluated by RT-PCR in the testing set. Event-Free-Survival (EFS) according to ct-miRNA signatures was estimated by Kaplan-Meier method and Cox regression model. Results: In the training set, starting from 51 ct-miRNAs associated with pCR, six signatures with statistically significant predictive capability in terms of Area Under the ROC curve (AUC) were identified. Four signatures were confirmed in the testing set: Lapatinib at T0 and T1, (AUC 0.86 [95%CI 0.73-0.98] and 0.71 [0.55-0.86]), respectively; Trastuzumab at T1 (0.81 [0.70-0.92]); Lapatinib+Trastuzumab at T1 (0.67 [0.51-0.83]). These signatures were confirmed predictive after adjusting for known variables, including estrogen receptor status. ct-miRNA signatures failed to correlate with EFS. However, the levels of ct-miR-140-5p, included in the Trastuzumab signature, were associated with EFS (HR 0.43; 95%CI:0.22-0.84). Conclusions: ct-miRNAs discriminate patients with and without pCR after neoadjuvant Lapatinib- and/or Trastuzumab-based therapy. ct-miRNAs at week two could be valuable to identify patients responsive to Trastuzumab, to avoid unnecessary combination with other anti-HER2 agents, and finally to assist de-escalating treatment strategies.
Circulating microRNA (ct-miRNAs) are able to identify patients with differential response to HER2-targeted therapy. However, their dynamics are largely unknown. We assessed 752 miRNAs from 52 NeoALTTO patients with plasma pairs prior and two weeks after trastuzumab. Increased levels of ct-miR-148a-3p and ct-miR-374a-5p were significantly associated with pathological complete response (pCR) (p = 0.008 and 0.048, respectively). At a threshold ≥ the upper limit of the 95%CI of the mean difference, ...
Breast cancer is the second most common cause of deaths reported in women worldwide, and therefore there is a need to identify breast cancer patients at an early stage as timely diagnosis would help in effective management and appropriate monitoring of patients. Nevertheless, it is challenging to achieve these goals due to the lack of a specific biomarker for early detection and monitoring in breast cancer. Recently, microRNAs (miRNAs) have emerged as master regulators of the molecular pathways ...
#2Wei Lin(FJUTCM: Fujian University of Traditional Chinese Medicine)H-Index: 1
Last. Hang Fai Kwok(UM: University of Macau)H-Index: 23
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Engagement of programmed death-ligand 1 (PD-L1) with its receptor programmed death 1 (PD-1) on T cells has been speculated to play a major role in suppressing the immune system, which helps tumor cells evade anti-tumor immunity. With the development of whole genome sequencing technologies, microRNAs have gained more attention as an important new layer of molecular regulation. Recent studies have revealed that altered expression of microRNAs play a pivotal role in immune checkpoint and various ce...
Last. Yongqing Lai(PKU: Peking University)H-Index: 4
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: As influencing factors of genesis and progression in several types of human tumor, microRNAs (miRs) serves roles in the regulation of tumor cell viability, migration, and apoptosis. The present research aimed to investigate the association between the function of miR‑100‑5p and renal cell carcinoma (RCC). miR‑100‑5p expression was determined in RCC tissue and paired normal tissue samples using reverse transcription‑quantitative polymerase chain reaction. To assess the effects of miR‑100‑5p on ...
The development of predictive biomarkers is complex and the non-systematic approach to biomarker development in HER2-positive breast cancer challenges the way translational research is performed. Women with very favourable prognostic features will likely prefer shorter courses of treatment and might enquire about the possibility to forego aggressive chemotherapy. Considering these legitimate needs, Gingras et al. review the results of more than a decade of translational research efforts in this ...
Last. Jun Mao(Dalian Medical University)H-Index: 19
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MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in...
Last. José Baselga(University of Milan)H-Index: 177
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BackgroundPertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. MethodsWe...
512Background: In the neoadjuvant NeoALTTO trial dual HER2 blockade with lapatinib (L) plus trastuzumab (T) combined with weekly paclitaxel significantly increased the pathologic complete response rate (pCR) compared with either anti-HER2 agent alone plus paclitaxel. At first analysis pts with pCR had a better event free survival (EFS) and overall survival (OS) after median follow-up of 3.84 yrs. Methods: 455 pts with operable HER2-positive breast cancer were randomized to receive either L (n=15...
This study compares next-generation sequencing (NGS) technologies that have been optimized specifically for biofluid samples, with more established qPCR-based methods for profiling microRNAs in biofluids. The same patient serum samples were analyzed by NGS and qPCR, and differences in the serum microRNA profile between HBV and HCV infected patients were investigated. While there was overall good agreement between NGS and qPCR, there were some differences between the platforms, highlighting the i...
#1Fengzhou Du(Peking Union Medical College)H-Index: 3
Last. B H Xu(Peking Union Medical College)H-Index: 8
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Approximately 20% of HER2 positive breast cancer develops disease recurrence after adjuvant trastuzumab treatment. This study aimed to develop a molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence. Using miRNA microarrays, nine miRNAs that differentially expressed between the recurrent and non-recurrent patients were identified. Then, we validated the expression of these miRNAs using qRT-PCR in training set (n = 101), and generated a 2-miRNA (m...
Active surveillance (AS) has evolved as a strategy alternative to radical treatments for very low risk and low-risk prostate cancer (PCa). However, current criteria for selecting AS patients are still suboptimal. Here, we performed an unprecedented analysis of the circulating miRNome to investigate whether specific miRNAs associated with disease reclassification can provide risk refinement to standard clinicopathological features for improving patient selection. The global miRNA expression profi...
#2Sina Taefehshokr(Tabriz University of Medical Sciences)H-Index: 8
Last. Behzad Baradaran(Tabriz University of Medical Sciences)H-Index: 41
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Abstract Characterized by remarkable levels of aggression and malignancy, BC remains one of the leading causes of death in females world wide. Accordingly, significant efforts have been made to develop early diagnostic tools, increase treatment efficacy, and improve patient prognosis. Hopefully, many of the molecular mechanisms underlying BC have been detected and show promising targeting potential. In particular, short and long non-coding RNAs (ncRNAs) are a class of endogenous BC controllers a...
The functional involvement of microRNAs in human neoplasia has raised in the last years an increasing interest in the scientific community toward the potential application in clinics as therapeutic tools. Indeed, the possibility to modulate their expression to re-establish a lost equilibrium and counteract tumor growth and dissemination, and/or to improve responsiveness to standard therapies, is promising and fascinating. However, several issues need to be taken into account such as factors rela...
ObjectThe current study was performed to construct a model with microRNA (miRNA/miR) expression profile and TNM staging system for prognosis predicting in patients with lung adenocarcinoma (LUAD). MethodsDifferentially expressed miRNAs were identified from miRNA data of LUAD in The Cancer Genome Atlas (TCGA) database. Potential prognostic miRNAs and TNM classification parameters, screened out by Cox proportional hazards regression analysis, were included in the prognostic model. The prognostic m...
PURPOSE This study aimed to investigate the predictive and prognostic roles of circulating exosomal miRNAs in breast cancer treated with trastuzumab-based chemotherapy. METHODS Circulating exosomal miRNAs from trastuzumab-resistant (n = 4) and -sensitive (n = 4) patients were profiled using miRNA microarray. The predictive and prognostic roles of filtered miRNAs were validated in 107 early-stage and 68 metastatic patients treated with trastuzumab-based chemotherapy through receiver-operating cha...
PURPOSE Overexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer. METHODS miR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either ...
HER2-positive breast cancers that achieve pathological complete response (pCR) after HER2-directed therapy consistently have good survival. We previously identified HSD17B4 methylation as a marker for pCR by methylation screening. Here, we aimed to identify a new marker by conducting a multi-omics analysis of materials prepared by laser capture microdissection, and adding 71 new samples. In the screening set (n = 36), mutations, methylation, and expression were analyzed by targeted sequencing, I...
#2Xinyue Liu(TMUCIH: Tianjin Medical University Cancer Institute and Hospital)H-Index: 3
Last. Jilong Yang(TMUCIH: Tianjin Medical University Cancer Institute and Hospital)H-Index: 21
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The diagnosis, treatment and prognosis of sarcoma are mainly dependent on tissue biopsy, which is limited in its ability to provide a panoramic view into the dynamics of tumor progression. In addition, effective biomarkers to monitor the progression and therapeutic response of sarcoma are lacking. Liquid biopsy, a recent technological breakthrough, has gained great attention in the last few decades. Nucleic acids (such as DNA, mRNAs, microRNAs, and long non-coding RNAs) that are released from tu...
Last. Michael J. Kerin(National University of Ireland, Galway)H-Index: 83
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Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-19...
Prostate cancer (PCa) represents the most commonly diagnosed neoplasm among men. miRNAs, as biomarkers, could further improve reliability in distinguishing malignant versus nonmalignant, and aggressive versus nonaggressive PCa. However, conflicting data was reported for certain miRNAs, and there was a lack of consistency and reproducibility, which has been attributed to diverse (pre)analytical factors. In order to address current challenges in miRNA clinical research on PCa, a PubMed-based liter...